BackgroundPostnatal endothelial progenitor cells (EPCs) have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated.ResultsIn an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels.Mouse lung microvascular endothelial cells (MLMVECs) were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony). These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs) in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels.ConclusionThe lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

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The ban of antibiotics as a feed additive requires alternatives to stabilize the health and performance particularly of the young animals. Essential oils obtained from fennel seed (Foeniculi aetheroleum) and caraway seed (Carvi aetheroleum) were tested in diets for weaned piglets in comparison with either a diet without feed additive or with a combination of formic acid and copper (positive control). Four groups of sixteen piglets (live weight 7 kg, age 26 days) received diets without (1) or with supplements of 7.5 g formic acid + 160 mg Cu/kg (2), 100 mg fennel oil/kg (3) or 100 mg caraway oil/kg (4) during 3 weeks after weaning. In the subsequent 4 weeks, all piglets were fed a diet without these additions. Fennel oil contained almost 2/3 anethol, approximately 1/5 fenchon and the remaining part consisting of alpha + beta-pinen, limonen (p-mentha-1,8-dien) and estragol. In the caraway oil, half of the contents was represented by limonen and the other half by carvon. There were no piglet losses and only few cases of diarrhoea. The combination of formic acid and copper increased feed consumption by 27% and daily weight gain by 25%. There were no differences in the performance between the group fed fennel oil and the control without additives. Piglets fed caraway oil tended to consume less feed and to gain approximately 10% less. In feed choice experiments, pigs consumed the same two diets from two troughs with 50% of total feed amount, as expected. The diets containing fennel or caraway oils were consumed at less than 50%. If the diet contained 100 mg fennel oil/kg, the decrease of percentual feed intake was significant. The results of the feeding experiment and of the feed choice experiment question the classification of fennel and caraway oils as flavour additives or as 'appetite promoters' in diets for weaned piglets.

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Objective: Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1 blockade). Meanwhile, the FDA approved PD-1/PD-L1 inhibition treatment for any solid tumor showing MSI and/or defects in the MMR system. For squamous cell carcinoma (SCC) of the penis, no data on the frequency of MSI and altered MMR protein expression are available to date. Therefore, we investigated the MSI status and the expression of MMR proteins in a large cohort of penile SCCs. Methods: The MSI status of 105 archival formalin-fixed, paraffin-embedded penile SCCs was analyzed using the 5 markers of the NCI consensus panel for MIS testing (BAT25, 26, D2S123, D17S250, and D5S346), or, in cases without representative nontumorous tissue using a validated panel of 5 quasimonomorphic mononucleotide repeat markers (BAT 25, 26 and NR21, 24, 27). The expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 was analyzed using immunohistochemistry and a tissue microarray of a subset of penile SCCs from our cohort (n = 75). Results: Overall, in 96/105 cases, at least 4 microsatellite markers gave interpretable results. None of the cases showed MSI. Immunohistochemistry for MMR proteins was analyzable in 70/75 cases. All cases showed a regular expression of the MMR proteins. Conclusion: MSI and defects in MMR protein expression are not regular features of penile SCC and might not act as biomarkers for PD-1/PD-L1 blockade therapy in penile carcinoma.